publication . Article . 2018

Novel imidazopyridine suppresses STAT3 activation by targeting SHP-1

Su, Jung-Chen; Chang, Chuan-Hsun; Wu, Szu-Hsien; Shiau, Chung-Wai;
Open Access English
  • Published: 01 Sep 2018 Journal: Journal of Enzyme Inhibition and Medicinal Chemistry (issn: 1475-6366, eissn: 1475-6374, Copyright policy)
  • Publisher: Taylor & Francis Group
Abstract
Abstract The unregulated activation of STAT3 has been demonstrated to occur in many cancers and enhances tumour growth, migration, and invasion. Stimulation by cytokines, growth factors, and hormones triggers this activation by phosphorylating STAT3 at tyrosine 705. Novel imidazopyridine compounds were synthesized to evaluate the inhibition of STAT3 at Y705. Among the tested compounds, 16 reduced the level of phospho-STAT3, inhibited the downstream signalling cascade and subsequently attenuated the survival of hepatocellular carcinoma (HCC) cells. Further assays showed that the reduction effects of compound 16 on tyrosine 705 of STAT3 were attributed to up-regul...
Subjects
free text keywords: STAT3, SHP-1, HCC, imidazopyridine, Therapeutics. Pharmacology, RM1-950, Article, Pharmacology, Drug Discovery, General Medicine, Chemistry, Stimulation, Biochemistry, Hormone, Cancer research, biology.protein, biology
28 references, page 1 of 2

1 Yu H, Lee H, Herrmann A, et al.Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer 2014;14:736–46.25342631 [PubMed]

2 Zhong Z, Wen Z, Darnell JE.Jr., Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994;264:95–8.8140422 [OpenAIRE] [PubMed]

3 Lee H, Deng J, Kujawski M, et al.STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med 2010;16:1421–8.21102457 [OpenAIRE] [PubMed]

4 Xin H, Lu R, Lee H, et al.G-protein-coupled receptor agonist BV8/prokineticin-2 and STAT3 protein form a feed-forward loop in both normal and malignant myeloid cells. J Biol Chem 2013;288:13842–9.23548897 [OpenAIRE] [PubMed]

5 Eyking A, Ey B, Runzi M, et al.Toll-like receptor 4 variant D299G induces features of neoplastic progression in Caco-2 intestinal cells and is associated with advanced human colon cancer. Gastroenterology 2011;141:2154–65.21920464 [OpenAIRE] [PubMed]

6 Nielsen M, Kaestel CG, Eriksen KW, et al.Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells. Leukemia 1999;13:735–8.10374878 [PubMed]

7 Bhattacharya S, Ray RM, Johnson LR STAT3-mediated transcription of Bcl-2, Mcl-1 and c-IAP2 prevents apoptosis in polyamine-depleted cells. Biochem J 2005;392:335–44.16048438 [OpenAIRE] [PubMed]

8 Su JC, Mar AC, Wu SH, et al.Disrupting VEGF-A paracrine and autocrine loops by targeting SHP-1 suppresses triple negative breast cancer metastasis. Sci Rep 2016;6:28888.27364975 [OpenAIRE] [PubMed]

9 den Hertog J, Ostman A, Bohmer FD Protein tyrosine phosphatases: regulatory mechanisms. FEBS J 2008;275:831–47.18298791 [OpenAIRE] [PubMed]

10 Yamada S, Shiono S, Joo A, Yoshimura A Control mechanism of JAK/STAT signal transduction pathway. FEBS Lett 2003;534:190–6.12527385 [PubMed]

11 Huang S, Chen M, Shen Y, et al.Inhibition of activated Stat3 reverses drug resistance to chemotherapeutic agents in gastric cancer cells. Cancer Lett 2012;315:198–205.22104727 [PubMed]

12 Prabhu VV, Hong B, Allen JE, et al Small-molecule prodigiosin restores p53 tumor suppressor activity in chemoresistant colorectal cancer stem cells via c-Jun-mediated ΔNp73 inhibition and p73 activation. Cancer Res 2016;76:1989–99.26759239 [PubMed]

13 Mott JL, Bronk SF, Mesa RA, et al.BH3-only protein mimetic obatoclax sensitizes cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Mol Cancer Ther 2008;7:2339–47.18723481 [OpenAIRE] [PubMed]

14 Nguyen M, Marcellus RC, Roulston A, et al.Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci USA 2007;104:19512–7.18040043 [OpenAIRE] [PubMed]

15 Llagostera E, Soto-Cerrato V, Joshi R, et al.High cytotoxic sensitivity of the human small cell lung doxorubicin-resistant carcinoma (GLC4/ADR) cell line to prodigiosin through apoptosis activation. Anticancer Drugs 2005;16:393–9.15746575 [PubMed]

28 references, page 1 of 2
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publication . Article . 2018

Novel imidazopyridine suppresses STAT3 activation by targeting SHP-1

Su, Jung-Chen; Chang, Chuan-Hsun; Wu, Szu-Hsien; Shiau, Chung-Wai;